Publications by authors named "Frank B Hu"

1,258 Publications

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A healthy plant-based diet is favorably associated with cardiometabolic risk factors among participants of South Asian ancestry.

Am J Clin Nutr 2022 Jun 22. Epub 2022 Jun 22.

Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Background: Plant-based diets are recommended for chronic disease prevention, yet there has been little focus on plant-based diet quality among participants of South Asian ancestry who consume a predominantly plant-based diet.

Objective: We evaluated cross-sectional and prospective associations between plant-based diet quality and cardiometabolic risk among participants of South Asian ancestry who are living in the US.

Design: We included 891 participants of South Asian ancestry who completed the baseline visit in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. The prospective analysis included 735 participants who completed exam 2 (∼5 y after baseline). Plant-based diet quality was assessed using 3 indices - an overall plant-based diet index (PDI) that summarizes the consumption of plant foods, a healthful PDI (hPDI) that measures consumption of healthy plant foods, and an unhealthful PDI (uPDI) that reflects consumption of less-healthy plant foods.

Results: At baseline, the PDI was inversely associated with fasting glucose. We observed an inverse association between PDI and hPDI with HOMA-IR, LDL-C, weight, and BMI (all P<0.05). Higher scores on the hPDI, but not PDI, were associated with lower glycated hemoglobin, higher adiponectin, lower visceral fat area and pericardial fat volume. Each 5-unit higher hPDI was associated with a lower likelihood of fatty liver (odds ratio [OR] 0.76 [95% CI: 0.64, 0.90]), and obesity (OR 0.88 [95% confidence interval (CI): 0.80, 0.97]). There were no associations between uPDI and cardiometabolic risk. Prospectively, after covariate adjustment for baseline values, each 5-unit higher hPDI was associated with an 18% lower risk of incident type 2 diabetes (OR 0.82 [95% CI: 0.67, 1.00]).

Conclusions: A higher intake of healthful plant-based foods was associated with a favorable cardiometabolic risk profile. Dietary recommendations to lower chronic disease risk among participants of South Asian ancestry should focus on the quality of plant-based foods.
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http://dx.doi.org/10.1093/ajcn/nqac174DOI Listing
June 2022

Intergenerational Transmission of Obesity from Mothers to Their Offspring: Trends and Associated Factors Derived from the Malaysian National Health and Morbidity Survey (NHMS).

Nutrients 2022 May 24;14(11). Epub 2022 May 24.

Institute of Medical Research, Ministry of Health Malaysia, Jalan Pahang, Kuala Lumpur 50588, Malaysia.

Along with the increasing overweight and obesity trends among adults and children globally, numerous studies have suggested a strong association between maternal overweight and obesity among their offspring. We sought to report the prevalence and associated factors of intergenerational overweight and obesity among mother-child pairs in Malaysia from 2006 to 2015. Data were analysed from three waves of the Malaysian National Health and Morbidity Survey, a population-based cross-sectional study conducted in 2006, 2011 and 2015. A mother and the youngest child from each household formed 'mother-child pairs' and were grouped according to their body mass index categories. A multivariable logistic regression model was performed to determine the factors associated with overweight mother/overweight child pairs (OWM/OWC), with normal weight mother/normal weight child pairs (NWM/NWC) as the reference group. The prevalence of OWM/OWC increased from 15.3% to 21.7%, while the prevalence of NWM/NWC decreased from 28.4% to 23.8% between 2006 and 2015. Older maternal age and having primary and secondary education levels were positively associated with OWM/OWC. Conversely, older child age, Chinese ethnicity, large household size and low-income households were inversely associated with OWM/OWC. In conclusion, intergenerational weight gain is a worrisome trend in Malaysia. These findings may help in guiding priority setting for obesity prevention strategies in Malaysia.
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http://dx.doi.org/10.3390/nu14112186DOI Listing
May 2022

Intake of whole grain foods and risk of coronary heart disease in US men and women.

BMC Med 2022 06 10;20(1):192. Epub 2022 Jun 10.

Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.

Background: Epidemiological studies have demonstrated a favorable association of whole grain intake with coronary heart disease (CHD) risk, although whether such an inverse association holds true for individual whole grain foods that have various nutritional profiles has not been examined.

Methods: We followed 74,244 women from Nurses' Health Study since 1986, 91,430 women from Nurses' Health Study II since 1991, and 39,455 men from the Health Professionals Follow-Up Study since 1984, who did not have a history of cardiovascular disease or cancer at baseline. Intake of seven individual whole grain foods was repeatedly assessed using a validated semi-quantitative food frequency questionnaire every 2-4 years since baseline. CHD diagnoses were ascertained through review of medical records or death certificates.

Results: We documented 9461 CHD cases during an average of 25.8 years' follow-up. In the multivariable-adjusted model, the pooled hazard ratio (HR) (95% CI) of CHD risk corresponding to each one serving/day consumption of total whole grains was 0.93 (0.90-0.95; p trend <0.0001). Higher consumption of most individual whole grain foods was associated with significantly lower risk of CHD. Comparing participants consuming ≥1 serving/day with those consuming < 1 serving/month, the multivariable-adjusted pooled HRs (95% CIs) of CHD were 0.83 (0.78-0.89) for whole grain cold breakfast cereal, 0.92 (0.86-0.99) for dark bread, and 1.08 (0.96-1.22) for popcorn. For other whole grain foods with lower overall intake levels, comparing intake level of ≥2 servings/week with < 1 serving/month, the pooled hazard ratios (95% CIs) were 0.79 (0.74-0.84) for oatmeal, 0.79 (0.71-0.87) for brown rice, 0.84 (0.78-0.90) for added bran, and 0.87 (0.77-0.99) for wheat germ. Cubic spline regression suggested non-linear associations for certain whole grain foods: the risk reduction plateaued approximately over 2 servings/day for total whole grains, 0.5 serving/day for both cold breakfast cereal and dark bread, 0.5 serving/week for oatmeal, 1 serving/week for brown rice, and 2 serving/week for added bran (p for non-linearity <0.01 for all associations).

Conclusions: These data suggest that higher consumption of total whole grains, as well as individual whole grain foods except popcorn, were significantly associated with lower CHD risk. The inverse associations may plateau at various intake levels for total whole grain and individual whole grain foods. This study provides further evidence in support of increasing whole grain intake for the prevention of CHD in US populations.
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http://dx.doi.org/10.1186/s12916-022-02396-zDOI Listing
June 2022

Daily Urinary Sodium and Potassium Excretion and Cardiovascular Risk. Reply.

N Engl J Med 2022 06;386(22):e60

Harvard T.H. Chan School of Public Health, Boston, MA.

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http://dx.doi.org/10.1056/NEJMc2203785DOI Listing
June 2022

Intrapersonal Stability of Plasma Metabolomic Profiles over 10 Years among Women.

Metabolites 2022 Apr 20;12(5). Epub 2022 Apr 20.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

In epidemiological studies, samples are often collected long before disease onset or outcome assessment. Understanding the long-term stability of biomarkers measured in these samples is crucial. We estimated within-person stability over 10 years of metabolites and metabolite features ( = 5938) in the Nurses' Health Study (NHS): the primary dataset included 1880 women with 1184 repeated samples donated 10 years apart while the secondary dataset included 1456 women with 488 repeated samples donated 10 years apart. We quantified plasma metabolomics using two liquid chromatography mass spectrometry platforms (lipids and polar metabolites) at the Broad Institute (Cambridge, MA, USA). Intra-class correlations (ICC) were used to estimate long-term (10 years) within-person stability of metabolites and were calculated as the proportion of the total variability (within-person + between-person) attributable to between-person variability. Within-person variability was estimated among participants who donated two blood samples approximately 10 years apart while between-person variability was estimated among all participants. In the primary dataset, the median ICC was 0.43 (1st quartile (Q1): 0.36; 3rd quartile (Q3): 0.50) among known metabolites and 0.41 (Q1: 0.34; Q3: 0.48) among unknown metabolite features. The three most stable metabolites were N6,N6-dimethyllysine (ICC = 0.82), dimethylguanidino valerate (ICC = 0.72), and N-acetylornithine (ICC = 0.72). The three least stable metabolites were palmitoylethanolamide (ICC = 0.05), ectoine (ICC = 0.09), and trimethylamine-N-oxide (ICC = 0.16). Results in the secondary dataset were similar (Spearman correlation = 0.87) to corresponding results in the primary dataset. Within-person stability over 10 years is reasonable for lipid, lipid-related, and polar metabolites, and varies by metabolite class. Additional studies are required to estimate within-person stability over 10 years of other metabolites groups.
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http://dx.doi.org/10.3390/metabo12050372DOI Listing
April 2022

Stability and reproducibility of proteomic profiles in epidemiological studies: comparing the Olink and SOMAscan platforms.

Proteomics 2022 May 21:e2100170. Epub 2022 May 21.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Limited data exist on the performance of high-throughput proteomics profiling in epidemiological settings, including the impact of specimen collection and within-person variability over time. Thus, the Olink (972 proteins) and SOMAscan7Kv4.1 (7322 proteoforms of 6596 proteins) assays were utilized to measure protein concentrations in archived plasma samples from the Nurses' Health Studies and Health Professionals Follow-Up Study. Spearman's correlation coefficients (r) and intraclass correlation coefficients (ICCs) were used to assess agreement between (1) 42 triplicate samples processed immediately, 24-h or 48-h after blood collection from 14 participants; and (2) 80 plasma samples from 40 participants collected 1-year apart. When comparing samples processed immediately, 24-h, and 48-h later, 55% of assays had an ICC/r ≥ 0.75 and 87% had an ICC/r ≥ 0.40 in Olink compared to 44% with an ICC/r ≥ 0.75 and 72% with an ICC/r ≥ 0.40 in SOMAscan7K. For both platforms, >90% of the assays were stable (ICC/r ≥ 0.40) in samples collected 1-year apart. Among 817 proteins measured with both platforms, Spearman's correlations were high (r > 0.75) for 14.7% and poor (r < 0.40) for 44.8% of proteins. High-throughput proteomics profiling demonstrated reproducibility in archived plasma samples and stability after delayed processing in epidemiological studies, yet correlations between proteins measured with the Olink and SOMAscan7K platforms were highly variable.
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http://dx.doi.org/10.1002/pmic.202100170DOI Listing
May 2022

Caffeine consumption and cardiovascular health.

Nat Rev Cardiol 2022 Jul;19(7):429-430

Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1038/s41569-022-00719-4DOI Listing
July 2022

Arginine catabolism metabolites and atrial fibrillation or heart failure risk: two case-control studies within the PREDIMED trial.

Am J Clin Nutr 2022 May 16. Epub 2022 May 16.

University of Navarra, Department of Preventive Medicine and Public Health, Pamplona, Spain.

Background: Arginine-derived metabolites are involved in oxidative and inflammatory processes related with endothelial function and cardiovascular risk.

Objective: To prospectively examine the associations of arginine catabolism metabolites with the risk of atrial fibrillation (AF) or heart failure (HF), and to evaluate the potential modification of these associations through Mediterranean diet (MedDiet) interventions in a large primary prevention trial.

Methods: Two nested matched case-control studies were designed within the PREDIMED trial. Five hundred and nine incident cases and 547 matched controls for the AF case-control study, and 326 cases and 402 matched controls for the HF case-control study participants were selected using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using liquid chromatography tandem mass spectrometry. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups vs control group) were analyzed with the likelihood ratio test.

Results: Inverse associations with incident AF were observed for arginine [OR per 1 SD (95% CI): 0.83 (0.73, 0.94)]) and homoarginine [0.87 (0.76, 0.98)], whereas positive associations were found for the asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA) [1.15 (1.01, 1.31)] and citrulline [1.19 (1.01, 1.39)]. For HF, inverse associations were found for arginine [0.82 (0.69, 0.97)] and homoarginine [0.81 (0.68, 0.96)], and positive associations for the ADMA/SDMA ratio [1.19 (1.02, 1.41)], N1-acetylspermidine [1.34 (1.12, 1.60)], and diacetylspermine [1.20 (1.02, 1.41)]. In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (p for interaction 0.044).

Conclusions: Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF.This trial was registered at controlled-trials.com as ISRCTN35739639.
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http://dx.doi.org/10.1093/ajcn/nqac139DOI Listing
May 2022

Excess mortality associated with elevated body weight in the USA by state and demographic subgroup: A modelling study.

EClinicalMedicine 2022 Jun 28;48:101429. Epub 2022 Apr 28.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: The obesity epidemic in the USA continues to grow nationwide. Although excess weight-related mortality has been studied in general, less is known about how it varies by demographic subgroup within the USA. In this study we estimated excess mortality associated with elevated body weight nationally and by state and subgroup.

Methods: We developed a nationally-representative microsimulation (individual-level) model of US adults between 1999 and 2016, based on risk factor data from 6,002,012 Behavioral Risk Factor Surveillance System respondents. Prior probability distributions for hazard ratios relating body-mass index (BMI) to mortality were informed by a global pooling dataset. Individual-level mortality risks were modelled accounting for demographics, smoking history, and BMI adjusted for self-report bias. We calibrated the model to empirical all-cause mortality rates from CDC WONDER by state and subgroup, and assessed the predictive accuracy of the model using a random sample of data withheld from model fitting. We simulated counterfactual scenarios to estimate excess mortality attributable to different levels of excess weight and smoking history.

Findings: We estimated that excess weight was responsible for more than 1300 excess deaths per day (nearly 500,000 per year) and a loss in life expectancy of nearly 2·4 years in 2016, contributing to higher excess mortality than smoking. Relative excess mortality rates were nearly twice as high for women compared to men in 2016 (21·9% vs 13·9%), and were higher for Black non-Hispanic adults. By state, overall excess weight-related life expectancy loss ranged from 1·75 years (95% UI 1·57-1·94) in Colorado to 3·18 years (95% UI 2·86-3·51) in Mississippi.

Interpretation: Excess weight has substantial impacts on mortality in the USA, with large disparities by state and subgroup. Premature mortality will likely increase as obesity continues to rise.

Funding: The JPB Foundation, NIH, CDC.
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http://dx.doi.org/10.1016/j.eclinm.2022.101429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065308PMC
June 2022

Changes in plasma total saturated fatty acids and palmitic acid are related to pro-inflammatory molecule IL-6 concentrations after nutritional intervention for one year.

Biomed Pharmacother 2022 Jun 25;150:113028. Epub 2022 Apr 25.

Department of Nutrition, Food Sciences and Gastronomy, XIA School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain. Electronic address:

Systemic inflammation is associated with an increased risk of non-communicable diseases, such as cardiovascular diseases and diabetes. Circulating fatty acids (FA) are known to be related to these conditions, possibly through their role in inflammation, although different types of FAs can have opposite effects on inflammatory mediators. The aim of the present study was to analyze the association of plasma FAs with inflammatory biomarkers in a PREDIMED trial subsample after one year of intervention. In a one-year longitudinal study of 91 participants of the PREDIMED trial (Barcelona-Clinic center), plasma FAs and inflammatory biomarkers were analyzed using gas chromatography and ELISA, respectively. In baseline plasma, a multivariable-adjusted ordinary least squares regression model showed that n-3 polyunsaturated FAs concentrations were inversely associated with concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin, whereas the level of the most abundant saturated FA, palmitic acid, was directly associated with concentrations of interleukin-6 (IL-6) (β = 0.48 pg/mL, 95% CI: 0.03, 0.93 per 1-SD increase, p-value = 0.037). After one year of nutritional intervention, changes of plasma diet-derived total saturated FAs and palmitic acid were directly associated with changes in IL-6 (β = 0.59 pg/mL [95% CI: 0.28, 0.89] per 1-SD, p-value = 0.001; β = 0.64 pg/mL, 95% CI: 0.31, 0.98, p-value = 0.001), respectively, after correction for multiple testing. Our findings suggest that saturated FAs of dietary origin, especially palmitic acid, are directly involved in the increase of IL-6 in plasma.
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http://dx.doi.org/10.1016/j.biopha.2022.113028DOI Listing
June 2022

Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts.

PLoS Med 2022 04 26;19(4):e1003972. Epub 2022 Apr 26.

Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts, United States of America.

Background: Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes.

Methods And Findings: We analyzed data from 35,759 men and women in the United States participating in the Nurses' Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data.

Conclusions: These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.
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http://dx.doi.org/10.1371/journal.pmed.1003972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041832PMC
April 2022

Plasma metabolite profiles related to plant-based diets and the risk of type 2 diabetes.

Diabetologia 2022 Jul 8;65(7):1119-1132. Epub 2022 Apr 8.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Aims/hypothesis: Plant-based diets, especially when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes. However, whether plasma metabolite profiles related to plant-based diets reflect this association was unknown. The aim of this study was to identify the plasma metabolite profiles related to plant-based diets, and to evaluate the associations between the identified metabolite profiles and the risk of type 2 diabetes.

Methods: Within three prospective cohorts (Nurses' Health Study, Nurses' Health Study II and Health Professionals Follow-up Study), we measured plasma metabolites from 10,684 participants using high-throughput LC MS. Adherence to plant-based diets was assessed by three indices derived from the food frequency questionnaire: an overall Plant-based Diet Index (PDI), a Healthy Plant-based Diet Index (hPDI), and an Unhealthy Plant-based Diet Index (uPDI). Multi-metabolite profiles related to plant-based diet were identified using elastic net regression with a training/testing approach. The prospective associations between metabolite profiles and incident type 2 diabetes were evaluated using multivariable Cox proportional hazards regression. Metabolites potentially mediating the association between plant-based diets and type 2 diabetes risk were further identified.

Results: We identified multi-metabolite profiles comprising 55 metabolites for PDI, 93 metabolites for hPDI and 75 metabolites for uPDI. Metabolite profile scores based on the identified metabolite profiles were correlated with the corresponding diet index (Pearson r = 0.33-0.35 for PDI, 0.41-0.45 for hPDI, and 0.37-0.38 for uPDI, all p<0.001). Metabolite profile scores of PDI (HR per 1 SD higher = 0.81 [95% CI 0.75, 0.88]) and hPDI (HR per 1 SD higher = 0.77 [95% CI 0.71, 0.84]) showed an inverse association with incident type 2 diabetes, whereas the metabolite profile score for uPDI was not associated with the risk. Mutual adjustment for metabolites selected in the metabolite profiles, including trigonelline, hippurate, isoleucine and a subset of triacylglycerols, attenuated the associations of diet indices PDI and hPDI with lower type 2 diabetes risk. The explainable proportion of PDI/hPDI-related diabetes risk by these metabolites ranged between 8.5% and 37.2% (all p<0.05).

Conclusions/interpretation: Plasma metabolite profiles related to plant-based diets, especially a healthy plant-based diet, were associated with a lower risk of type 2 diabetes among a generally healthy population. Our findings support the beneficial role of healthy plant-based diets in diabetes prevention and provide new insights for future investigation.
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http://dx.doi.org/10.1007/s00125-022-05692-8DOI Listing
July 2022

Insulin Resistance, Hyperglycemia, and Risk of Developing Obstructive Sleep Apnea in U.S. Men and Women.

Ann Am Thorac Soc 2022 Apr 6. Epub 2022 Apr 6.

Brigham and Women's Hospital, Division of Sleep and Circadian Disorders, Boston, Massachusetts, United States.

Rationale: Recent prospective studies suggest diabetes as a risk factor for the development of obstructive sleep apnea (OSA). However, the extent to which diabetes-related traits, such as hyperglycemia and insulin resistance, are related to OSA risk remains uncertain.

Objectives: To examine risk of developing OSA according to baseline levels of fasting insulin and hemoglobin A1c (HbA1c).

Methods: Participants from four prospective US cohorts were included: the Nurses' Health Study (NHS; 2002-2012), NHSII (1995-2013), the Health Professionals Follow-up Study (HPFS; 1996-2012) and the Multi-Ethnic Study of Atherosclerosis (MESA; 2000-2012). OSA was assessed by self-reported clinical diagnosis in NHS/NHSII/HPFS and by at-home polysomnography in MESA (defined as Apnea-Hypopnea Index≥30).

Results: Of 9,283 participants with fasting insulin data, 790 (8.5%) developed OSA over 10-18 years of follow-up. After adjusting for sociodemographic, lifestyle and co-morbidity factors, the odds ratio (OR) for incident OSA comparing the extreme quintiles of fasting insulin was 3.59 (95% CI: 2.67, 4.82; p-trend<0.0001). Of 6,342 participants with HbA1c data, 715 (11.3%) developed OSA. The comparable OR for HbA1c was 2.21 (95% CI: 1.69, 2.89; p-trend<0.0001). Additional adjustment for BMI and waist circumference attenuated the associations for fasting insulin (p-trend=0.005) and HbA1c (p-trend=0.03). In the fully-adjusted model simultaneously including both biomarkers, only fasting insulin but not HbA1c was associated with OSA risk.

Conclusion: Independent of obesity, insulin resistance may play a more important role than hyperglycemia in the pathogenesis of OSA. Given the limitation of using self-reported diagnosis to exclude baseline prevalent OSA cases, additional studies are needed to further establish the temporal relationship and assess whether improving insulin resistance may reduce OSA risk.
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http://dx.doi.org/10.1513/AnnalsATS.202111-1260OCDOI Listing
April 2022

Healthy Lifestyle Score Including Sleep Duration and Cardiovascular Disease Risk.

Am J Prev Med 2022 Jul 28;63(1):33-42. Epub 2022 Mar 28.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine Research, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Introduction: Although insufficient or prolonged sleep duration is associated with cardiovascular disease, sleep duration is not included in most lifestyle scores. This study evaluates the relationship between a lifestyle score, including sleep duration and cardiovascular disease risk.

Methods: A prospective analysis among 67,250 women in the Nurses' Health Study and 29,114 men in Health Professionals Follow-up Study (1986-2016) was conducted in 2021. Lifestyle factors were updated every 2-4 years using self-reported questionnaires. The traditional lifestyle score was defined as not smoking, having a normal BMI, being physically active (≥30 minutes/day of moderate physical activity), eating a healthy diet, and drinking alcohol in moderation. Low-risk sleep duration, defined as sleeping ≥6 to <8 hours/day, was included as an additional component in the updated lifestyle score. Cox proportional hazard regression models were used to estimate cardiovascular disease risk. The likelihood-ratio test and C-statistics were used to compare both scores.

Results: A total of 11,710 incident cardiovascular disease cases during follow-up were documented. The multivariable-adjusted hazard ratios comparing 6 with 0 low-risk factors in the healthy lifestyle score including sleep duration were 0.17 (95% CI=0.12, 0.23) for cardiovascular disease, 0.14 (95% CI=0.10, 0.21) for coronary heart disease, and 0.20 (95% CI=0.12, 0.33) for stroke. Approximately 66% (95% CI=56%, 75%) of cardiovascular disease, 67% (95% CI=54%, 77%) of coronary heart disease, and 62% (95% CI=42%, 76%) of stroke cases were attributable to poor adherence to a healthy lifestyle including sleep. Adding sleep duration to the score slightly increased the C-statistics from 0.64 (95% CI=0.63, 0.64) to 0.65 (95% CI=0.64, 0.65) (p<0.001).

Conclusions: Adopting a healthy lifestyle including sleep recommendations could substantially reduce the risk of cardiovascular disease in U.S. adults.
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http://dx.doi.org/10.1016/j.amepre.2022.01.027DOI Listing
July 2022

Healthful eating patterns, serum metabolite profile and risk of diabetes in a population-based prospective study of US Hispanics/Latinos.

Diabetologia 2022 Jul 31;65(7):1133-1144. Epub 2022 Mar 31.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Aims/hypothesis: We aimed to evaluate associations of multiple recommended dietary patterns (i.e. the alternate Mediterranean diet [aMED], the Healthy Eating Index [HEI]-2015 and the healthful Plant-based Diet Index [hPDI]) with serum metabolite profile, and to examine dietary-pattern-associated metabolites in relation to incident diabetes.

Methods: We included 2842 adult participants free from diabetes, CVD and cancer during baseline recruitment of the Hispanic Community Health Study/Study of Latinos. Metabolomics profiling of fasting serum was performed using an untargeted approach. Dietary pattern scores were derived using information collected by two 24 h dietary recalls. Dietary-pattern-associated metabolites were identified using multivariable survey linear regressions and their associations with incident diabetes were assessed using multivariable survey Poisson regressions with adjustment for traditional risk factors.

Results: We identified eight metabolites (mannose, γ/β-tocopherol, N1-methylinosine, pyrraline and four amino acids) that were inversely associated with all dietary scores. These metabolites were detrimentally associated with various cardiometabolic risk traits, especially insulin resistance. A score comprised of these metabolites was associated with elevated risk of diabetes (RR 1.54 [95% CI 1.29, 1.83]), and this detrimental association appeared to be attenuated or eliminated by having a higher score for aMED (p = 0.0001), HEI-2015 (p = 0.020) or hPDI (p = 0.023). For example, RR (95% CI) of diabetes for each SD increment in the metabolite score was 1.99 (1.44, 2.37), 1.67 (1.17, 2.38) and 1.08 (0.86, 1.34) across the lowest to the highest tertile of aMED score, respectively.

Conclusions/interpretation: Various recommended dietary patterns were inversely related to a group of metabolites that were associated with elevated risk of diabetes. Adhering to a healthful eating pattern may attenuate or eliminate the detrimental association between metabolically unhealthy serum metabolites and risk of diabetes.
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http://dx.doi.org/10.1007/s00125-022-05690-wDOI Listing
July 2022

Avocado Consumption and Risk of Cardiovascular Disease in US Adults.

J Am Heart Assoc 2022 04 30;11(7):e024014. Epub 2022 Mar 30.

Department of Nutrition Harvard T.H. Chan School of Public Health Boston MA.

Background Epidemiologic studies on the relationship between avocado intake and long-term cardiovascular disease (CVD) risk are lacking. Methods and Results This study included 68 786 women from the NHS (Nurses' Health Study) and 41 701 men from the HPFS (Health Professionals Follow-up Study; 1986-2016) who were free of cancer, coronary heart disease, and stroke at baseline. Diet was assessed using validated food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios and 95% CIs. A total of 14 274 incident cases of CVD (9185 coronary heart disease events and 5290 strokes) were documented over 30 years of follow-up. After adjusting for lifestyle and other dietary factors, compared with nonconsumers, those with analysis-specific higher avocado intake (≥2 servings/week) had a 16% lower risk of CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk of coronary heart disease (pooled hazard ratio, 0.79; 95% CI, 0.68-0.91). No significant associations were observed for stroke. Per each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80 (95% CI, 0.71-0.91). Replacing half a serving/day of margarine, butter, egg, yogurt, cheese, or processed meats with the equivalent amount of avocado was associated with a 16% to 22% lower risk of CVD. Conclusions Higher avocado intake was associated with lower risk of CVD and coronary heart disease in 2 large prospective cohorts of US men and women. The replacement of certain fat-containing foods with avocado could lead to lower risk of CVD.
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http://dx.doi.org/10.1161/JAHA.121.024014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075418PMC
April 2022

Dietary lignans, plasma enterolactone levels, and metabolic risk in men: exploring the role of the gut microbiome.

BMC Microbiol 2022 03 29;22(1):82. Epub 2022 Mar 29.

Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.

Background: The conversion of plant lignans to bioactive enterolignans in the gastrointestinal tract is mediated through microbial processing. The goal of this study was to examine the relationships between lignan intake, plasma enterolactone concentrations, gut microbiome composition, and metabolic risk in free-living male adults.

Results: In 303 men participating in the Men's Lifestyle Validation Study (MLVS), lignan intake was assessed using two sets of 7-day diet records, and gut microbiome was profiled through shotgun sequencing of up to 2 pairs of fecal samples (n = 911). A score was calculated to summarize the abundance of bacteria species that were significantly associated with plasma enterolactone levels. Of the 138 filtered species, plasma enterolactone levels were significantly associated with the relative abundances of 18 species at FDR < 0.05 level. Per SD increment of lignan intake was associated with 20.7 nM (SEM: 2.3 nM) higher enterolactone concentrations among participants with a higher species score, whereas the corresponding estimate was 4.0 nM (SEM: 1.7 nM) among participants with a lower species score (P for interaction < 0.001). A total of 12 plasma metabolites were also significantly associated with these enterolactone-predicting species. Of the association between lignan intake and metabolic risk, 19.8% (95%CI: 7.3%-43.6%) was explained by the species score alone, 54.5% (95%CI: 21.8%-83.7%) by both species score and enterolactone levels, and 79.8% (95%CI: 17.7%-98.6%) by further considering the 12 plasma metabolites.

Conclusion: We identified multiple gut bacteria species that were enriched or depleted at higher plasma levels of enterolactone in men. These species jointly modified the associations of lignan intake with plasma enterolactone levels and explained the majority of association between lignan intake and metabolic risk along with enterolactone levels and certain plasma metabolites.
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http://dx.doi.org/10.1186/s12866-022-02495-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966171PMC
March 2022

Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.

Diabetes Care 2022 04;45(4):1013-1024

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

Background: Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.

Purpose: To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.

Data Sources: We searched PubMed and Embase until 6 March 2021.

Study Selection: We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.

Data Extraction: Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.

Data Synthesis: A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate-corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69-0.90).

Limitations: Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.

Conclusions: Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.
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http://dx.doi.org/10.2337/dc21-1705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016744PMC
April 2022

Protein intake and risk of frailty among older women in the Nurses' Health Study.

J Cachexia Sarcopenia Muscle 2022 Jun 23;13(3):1752-1761. Epub 2022 Mar 23.

Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid-IdiPaz, Madrid, Spain.

Background: There is evidence that an overall healthy diet is associated with lower risk of frailty. However, the effect of diet composition, specifically the role of protein intake on frailty, is mostly unclear. The aim of this study was to evaluate the intake of protein, including total, plant, animal, and dairy protein, in relation to frailty incidence in a large cohort of older women.

Methods: We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Intake of protein was measured nine times during follow-up from 1980 until 2010. Frailty was defined as having at least three of the following five criteria from the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight (FRAIL) scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses, and weight loss of ≥5%. The occurrence of frailty was assessed every 4 years from 1992 up to 2014.

Results: During follow-up, we identified 13 279 incident cases of frailty. Women with a higher intake of plant protein had a lower risk of developing frailty after adjustment for all relevant confounders [relative risks across quintiles of consumption: 1.00, 0.94, 0.89, 0.86, and 0.86; P-trend < 0.001]. In contrast, those with a higher intake of animal protein intake had a higher risk of frailty [relative risks across quintiles of consumption: 1.00, 0.98, 0.99, 1.00, and 1.07; P-trend 0.04]. The intake of total and dairy protein showed no significant association with frailty in the full model. Substituting 5% of energy from plant protein intake at the expense of animal protein, dairy protein, or non-dairy animal protein was associated with 38% (29%, 47%), 32% (21%, 42%), and 42% (33%, 50%) reduced risk of frailty.

Conclusions: A higher intake of plant protein, but not animal or dairy protein, was associated with a lower risk of frailty. Substitution of plant protein for animal protein, especially non-dairy animal protein, was associated with lower risk of frailty.
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http://dx.doi.org/10.1002/jcsm.12972DOI Listing
June 2022

Degree of Adherence to Based Diet and Total and Cause-Specific Mortality: Prospective Cohort Study in the Million Veteran Program.

Public Health Nutr 2022 Mar 21:1-38. Epub 2022 Mar 21.

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA.

Objective: To examine the associations between adherence to plant-based diets and mortality.

Design: prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separate the healthy plant foods from less-healthy plant foods.

Setting: the VA Million Veteran Program.

Participants: 315,919 men and women aged 19 to 104 years who completed a food frequency questionnaire at the baseline.

Results: We documented 31,136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality [hazard ratio (HR) comparing extreme deciles =0.75, 95% confidence interval (CI): 0.71 to 0.79, Ptrend <0.001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles =0.64, 95% CI: 0.61 to 0.68, Ptrend <0.001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles =1.41, 95% CI: 1.33 to 1.49, Ptrend <0.001). Similar significant associations of PDI, hPDI, and uPDI were also observed for CVD and cancer mortality. The associations between the plant-based diet indices and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.

Conclusions: A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.
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http://dx.doi.org/10.1017/S1368980022000659DOI Listing
March 2022

Cumulative Lactation and Clinical Metabolic Outcomes at Mid-Life among Women with a History of Gestational Diabetes.

Nutrients 2022 Feb 3;14(3). Epub 2022 Feb 3.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women's Health Study (2012-2014; = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996-2002), we assessed associations of cumulative lactation duration (none, <6 months, 6-12 months, ≥12-24 months, and ≥24 months) with clinical metabolic outcomes (including type 2 diabetes [T2D], prediabetes, and obesity) and cardiometabolic biomarkers (including biomarkers of glucose/insulin metabolism, fasting lipids, inflammation, and anthropometrics) 9-16 years after enrollment when women were at mid-life. At follow-up, women were 43.9 years old (SD 4.6) with a BMI of 28.7 kg/m (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0-6, 6-12, 12-24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9-16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.
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http://dx.doi.org/10.3390/nu14030650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839876PMC
February 2022

Dietary Sodium and Potassium Intake and Risk of Non-Fatal Cardiovascular Diseases: The Million Veteran Program.

Nutrients 2022 Mar 7;14(5). Epub 2022 Mar 7.

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02111, USA.

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke.

Design, Setting And Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP).

Main Outcome Measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records.

Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99-1.21, trend = 0.01) for sodium and 0.87 (95% CI: 0.79-0.96, trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14-1.39, trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06-1.19) for MI and 1.11 (1.03-1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality.

Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.
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http://dx.doi.org/10.3390/nu14051121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912456PMC
March 2022

Association between a lifestyle-based healthy heart score and risk of frailty in older women: a cohort study.

Age Ageing 2022 02;51(2)

Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, and IdiPaz (Instituto de Investigación Sanitaria Hospital Universitario La Paz), Madrid, Spain.

Background: Evidence on the comprehensive role of lifestyle in frailty risk is scarce. To assess the association between a lifestyle-based Healthy Heart Score (HHS), which estimates the 20-year risk of cardiovascular disease (CVD), and risk of frailty among older women.

Methods: Prospective cohort study in 121,700 nurses from the USA participating at the Nurses' Health Study. This study included 68,416 women aged ≥60 year with a follow-up from 1990 to 2014. The HHS was computed using the gender-specific beta-coefficients of the nine lifestyle factors, including current smoking, high body mass index, low physical activity, lack of moderate alcohol intake and unhealthy diet. Frailty incidence was assessed every 4 years from 1992 to 2014 as having ≥3 of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses and weight loss ≥5%.

Results: During 22 years of follow-up, 11,041 total incident cases of frailty were ascertained. Compared to women in the lowest quintile of the HHS (lowest estimated CVD risk), the multivariable-adjusted hazard ratio of frailty across quintiles was: Q2:1.67 (95% confidence interval 1.53, 1.82); Q3: 2.34 (2.15, 2.53); Q4: 3.54 (3.28, 3.83) and Q5: 5.92 (5.48, 6.38); P-trend > 0.001. Results were consistent for each frailty criterion, among participants with 0 frailty criteria at baseline, when using only baseline exposure or in 6-year-, 10-year- and 14-year-exposure lagged analyses, and after excluding participants with diabetes and CVD at baseline.

Conclusions: The HHS, based on a set of modifiable-lifestyle factors, is strongly associated with risk of frailty in older women.
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http://dx.doi.org/10.1093/ageing/afab268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826375PMC
February 2022

The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases.

Nat Rev Endocrinol 2022 04 21;18(4):205-218. Epub 2022 Jan 21.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Sugar-sweetened beverages (SSBs) are a major source of added sugars in the diet. A robust body of evidence has linked habitual intake of SSBs with weight gain and a higher risk (compared with infrequent SSB consumption) of type 2 diabetes mellitus, cardiovascular diseases and some cancers, which makes these beverages a clear target for policy and regulatory actions. This Review provides an update on the evidence linking SSBs to obesity, cardiometabolic outcomes and related cancers, as well as methods to grade the strength of nutritional research. We discuss potential biological mechanisms by which constituent sugars can contribute to these outcomes. We also consider global trends in intake, alternative beverages (including artificially-sweetened beverages) and policy strategies targeting SSBs that have been implemented in different settings. Strong evidence from cohort studies on clinical outcomes and clinical trials assessing cardiometabolic risk factors supports an aetiological role of SSBs in relation to weight gain and cardiometabolic diseases. Many populations show high levels of SSB consumption and in low-income and middle-income countries, increased consumption patterns are associated with urbanization and economic growth. As such, more intensified policy efforts are needed to reduce intake of SSBs and the global burden of obesity and chronic diseases.
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http://dx.doi.org/10.1038/s41574-021-00627-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778490PMC
April 2022

Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years.

Dent J (Basel) 2022 Jan 7;10(1). Epub 2022 Jan 7.

Department of Biostatistics and Epidemiology, Graduate School of Public Health, Medical Sciences Campus, University of Puerto Rico, San Juan 00936-5067, Puerto Rico.

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40-65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (β = -1.6, = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (β = -1.4, = 0.022; β = -1.6, = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (β = -1.6, = 0.038; β = -1.9, = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period.
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http://dx.doi.org/10.3390/dj10010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774522PMC
January 2022

Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults.

J Am Coll Cardiol 2022 01;79(2):101-112

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Electronic address:

Background: Olive oil consumption has been shown to lower cardiovascular disease risk, but its associations with total and cause-specific mortality are unclear.

Objectives: The purpose of this study was to evaluate whether olive oil intake is associated with total and cause-specific mortality in 2 prospective cohorts of U.S. men and women.

Methods: The authors used multivariable-adjusted Cox proportional-hazards models to estimate HRs for total and cause-specific mortality among 60,582 women (Nurses' Health Study, 1990-2018) and 31,801 men (Health Professionals Follow-up Study, 1990-2018) who were free of cardiovascular disease or cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.

Results: During 28 years of follow-up, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among participants who had the highest consumption of olive oil (>0.5 tablespoon/day or >7 g/d) was 0.81 (95% CI: 0.78-0.84) compared with those who never or rarely consumed olive oil. Higher olive oil intake was associated with 19% lower risk of cardiovascular disease mortality (HR: 0.81; 95% CI: 0.75-0.87), 17% lower risk of cancer mortality (HR: 0.83; 95% CI: 0.78-0.89), 29% lower risk of neurodegenerative disease mortality (HR: 0.71; 95% CI: 0.64-0.78), and 18% lower risk of respiratory disease mortality (HR: 0.82; 95% CI: 0.72-0.93). In substitution analyses, replacing 10 g/d of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with 8%-34% lower risk of total and cause-specific mortality. No significant associations were observed when olive oil was compared with other vegetable oils combined.

Conclusions: Higher olive oil intake was associated with lower risk of total and cause-specific mortality. Replacing margarine, butter, mayonnaise, and dairy fat with olive oil was associated with lower risk of mortality.
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http://dx.doi.org/10.1016/j.jacc.2021.10.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851878PMC
January 2022

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

Am J Clin Nutr 2022 May;115(5):1270-1281

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Background: The effect of diet on age-related brain atrophy is largely unproven.

Objectives: We aimed to explore the effect of a Mediterranean diet (MED) higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy.

Methods: This 18-mo clinical trial longitudinally measured brain structure volumes by MRI using hippocampal occupancy score (HOC) and lateral ventricle volume (LVV) expansion score as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to follow 1) healthy dietary guidelines (HDG), 2) MED, or 3) Green-MED diet. All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The Green-MED group consumed green tea (3-4 cups/d) and Mankai (Wolffia-globosa strain, 100 g frozen cubes/d) green shake (+800 mg/d polyphenols).

Results: Among 284 participants (88% men; mean age: 51 y; BMI: 31.2 kg/m2; APOE-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared with younger participants, atrophy was accelerated among those ≥50 y old (HOC change: -1.0% ± 1.4% compared with -0.06% ± 1.1%; 95% CI: 0.6%, 1.3%; P < 0.001; LVV change: 3.2% ± 4.5% compared with 1.3% ± 4.1%; 95% CI: -3.1%, -0.8%; P = 0.001). In subjects ≥ 50 y old, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared with HDG (HOC: -0.8% ± 1.6% compared with -1.3% ± 1.4%; 95% CI: -1.5%, -0.02%; P = 0.042; LVV: 2.3% ± 4.7% compared with 4.3% ± 4.5%; 95% CI: 0.3%, 5.2%; P = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the parameter most strongly associated with brain atrophy attenuation (P < 0.05). Greater Mankai, green tea, and walnut intake and less red and processed meat were significantly and independently associated with reduced HOC decline (P < 0.05). Elevated urinary concentrations of the polyphenols urolithin-A (r = 0.24; P = 0.013) and tyrosol (r = 0.26; P = 0.007) were significantly associated with lower HOC decline.

Conclusions: A Green-MED (high-polyphenol) diet, rich in Mankai, green tea, and walnuts and low in red/processed meat, is potentially neuroprotective for age-related brain atrophy.This trial was registered at clinicaltrials.gov as NCT03020186.
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http://dx.doi.org/10.1093/ajcn/nqac001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071484PMC
May 2022

Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study.

EBioMedicine 2022 Jan 31;75:103799. Epub 2021 Dec 31.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Electronic address:

Background: Metabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk.

Methods: We conducted a nested T2D case-control study (n=244 cases, n=244 matched controls) within the Nurses' Health Study. Repeated metabolomics profiling (170 targeted metabolites) was conducted in participant blood specimens from 1989/1990 and 2000/2001, and T2D occurred between 2002 and 2008. We related 10-year metabolite changes (Δ-values) to subsequent T2D risk using conditional logistic models, adjusting for baseline metabolite levels and baseline levels and concurrent changes of BMI, diet quality, physical activity, and smoking status.

Findings: The 10-year changes of thirty-one metabolites were associated with subsequent T2D risk (false discovery rate-adjusted p-values [FDR]<0.05). The top three high T2D risk-associated 10-year changes were (odds ratio [OR] per standard deviation [SD], 95%CI): Δisoleucine (2.72, 1.97-3.79), Δleucine (2.53, 1.86-3.47), and Δvaline (1.93, 1.52-2.44); other high-risk-associated metabolite changes included alanine, tri-/diacylglycerol-fragments, short-chain acylcarnitines, phosphatidylethanolamines, some vitamins, and bile acids (ORs per SD between 1.31and 1.82). The top three low T2D risk-associated 10-year metabolite changes were (OR per SD, 95% CI): ΔN-acetylaspartic acid (0.54, 0.42-0.70), ΔC20:0 lysophosphatidylethanolamine (0.68, 0.56-0.82), and ΔC16:1 sphingomyelin (0.68, 0.56-0.83); 10-year changes of other sphingomyelins, plasmalogens, glutamine, and glycine were also associated with lower subsequent T2D risk (ORs per SD between 0.66 and 0.78).

Interpretation: Repeated metabolomics profiles reflecting the long-term deterioration of amino acid and lipid metabolism are associated with subsequent risk of T2D.
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http://dx.doi.org/10.1016/j.ebiom.2021.103799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733263PMC
January 2022

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Ann Intern Med 2022 04 4;175(4):574-589. Epub 2022 Jan 4.

National Heart, Lung, and Blood Institute, Bethesda, Maryland (S.C., Y.H.).

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.
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http://dx.doi.org/10.7326/M21-3729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018596PMC
April 2022
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